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1991 Fiscal Year Final Research Report Summary

Development of compounds to stimulate peripheral nerve regeneration viainduction of nerve growth factor synthesis.

Research Project

Project/Area Number 02454349
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionGifu Pharmaceutical University

Principal Investigator

FURUKAWA Shoei  Associate Professor, Department of Molecular Biology, Gifu Pharmaceutical University, 薬学部, 助教授 (90159129)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Nobuyuki  Assistant Professor, Department of Orthopedics, Jikei Medical School, 整形外科, 助手 (90198226)
Project Period (FY) 1990 – 1991
KeywordsNerve growth factor / Peripheral nerve / Nerve regeneration / Catechol compound / Axonal transport / Ganglion / Sympathetic neuron / Sensory neuron
Research Abstract

Nerve growth factor (NGF) is a protein that stimulates differentiation and maintains survival of sympathetic nerirons and some sensory neurons in peripheral nervous system. Recent works suggest important roles of NGF during peripheral nerve regeneration. This presents a possibility that NGF may be useful for a therapeutic or a promoting agent for nerve injury. We have already found that some kinds of catechol compounds can stimulate NGF synthesis in vitro. In this research, we aimed to evaluate the compounds with NGF synthesis stimulatory activity as stimulators of NGF synthesis in vivo. For this purpose, we screened various compounds and obtain a series of compounds, alkylcatechols, with potent stimulatory activity of NGF synthesis in vitro. Intraperitoneal administration of one of the alkylcatechols induced an increase in NGF protein and NGF mRNA in the adult rat heart and submaxillary gland. The increase in NGF protein was successively translocated from the sciatic nerve to sensory or sympathetic ganglia. Repetitive administration of an analogue of alkylcatechol caused significant elevations of substance P level in sensory ganglia and tyrosine hydroxylase activity in superior cervical ganglia of infant rats. These observations indicate that alkylcatechols can stimulate NGF synthesis in vivo and that the induced NGF has physiological effects on peripheral neurons. Therefore, we tested one of the alkylcatechols whether it can stimulate peripheral nerve regeneration. Daily injection of methylcatechol for 2 weeks increased the numbers of both myelinated and unmyelinated axons that grew across an 8mm gap after entubational repair of sectioned rat sciatic nerve.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Shigeno,T.,Mima,T.,Takakura,K.,Graham,D.I.,Kato,G.,Hashimoto,Y.,Furukawa,S.: "Amelioration of delayed neuronal death of the hippocampus by nerve growth factor." J.Neurosci.11. 2914-2919 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawagishi,H.,Ando,M.,Sakamoto,H.,Yoshida,S.,Ojima,F.,Ishiguro,Y.,Ukai,N.,Furukawa,S.: "Hericenones C,D and E,stimulators of nerve growth factor (NGF)-synthesis,from the mushroom Hericium erinaceum." Tetrahed.Lett.,. 32. 4561-4564 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hanaoka,Y.,Ohi,T.,Furukawa,Furukawa Y.,Hayashi K.and Matsukura,S.: "Effect of 4-methylcatechol on sciatic nerve growth factor level and motor nerve conduction velocity in experimental diabetic neuropathic process in rats." Exp.Neurol.115. 292-296 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishikawa,R.,Nishikori,K.,Furukawa,Y.,Hayashi,K.,Furukawa,S.: "Lesion-induced reduction of acidic fibroblast growth factor level in the distal part of rat sciatic nerve." Neurosci.Lett.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto,Y.,Kawatsura,H.Shiga,Y.,Furukawa,S.,Shigeno,T.: "Significance of nerve growth factor content levels after forebrain ischemia in gerbil." Neurosci.Lett.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 古川 昭栄,河岸 洋和: "神経成長因子の生理的意義とその合成促進物質" 化学と生物. 29. 640-646 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 古川 昭栄,古川 美子: "神経伝達物質updateー基礎から臨床まで(中村重信編)" 中外医学社, (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohi, T., Furukawa, S., Hayashi, K. and Matsukura, S.: "Ganglioside stimulation of nerve growth factor synthesis in cultured rat schwann cells." Biochem. Int.20. 739-746 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoda, I., Furukawa, Y. and Furukawa, S.: "Stimulation of nerve growth factor synthesis by propentofylline in cultured mouse astrogical cells." Biochem. Pharmacol.39. 1813-1816 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furukawa, Y., Fukazawa, N., Miyama, Y., Hayashi, K. and Furukawa, S.: "Stimulation of 4-alkylcatechol and their diacetylated derivatives on the synthesis of nerve growth factor." Biochem. Pharmacol.40. 2337-2342 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furukawa, S., Furukawa, Y.: "Nerve growth factor synthesis and its regulatory mechanisms : An approach to therapeutic induction of nerve growth factor synthesis." Cerebrovasc. Brain Metabol. Rev.2. 328-344 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shigeno, T., Mima, T., Takakura, K., Graham, D. I., Kato, G., Hashimoto, Y., Furukawa, S.: "Amelioration of delayed neuronal death of the hippocampus by nerve growth factor." J. Neurosci.11. 2914-2919 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawagishi, H., Ando, M., Sakamoto, H., Yoshida, S., Ojima, F., Ishiguro, Y., Ukai, N., Furukawa, S.: "hericenones C, D and E, stimulators of nerve growth factor (NGF) synthesis, form the mushroom Hericium erinaceus." Tetrahed. Lett.32. 4561-4564 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hanaoka, Y., Ohi, T., Furukawa, S., Furukawa Y., Hayashi, K. and Matsukura, S.: "Effect of 4-methylcatechol on sciatic nerve growth factor level and motor nerve conduction velocity in experimental diabetic neuropathic process in rats." Exp. Neurol.115. 292-296 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa, R., Nishikori, K., Furukawa, Y., Hayashi, K., Furukawa, S.: "Lesion-induced reduction of acidic fibroblast growth factor level in the distal part of rat sciatic nerve." Neurosci. Lett.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto, Y., Kawatsura, H., Shiga, Y., Furukawa, S., Shigeno, T.: "Significance of nerve growth factor content levels after forebrain ischemia in gerbil." Neurosci. Lett.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-16  

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